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Neoadjuvant Docetaxel Plus Cisplatin and 5-fluorouracil (TPF) Followed by Radiotherapy Plus Concomitant Chemo or Cetuximab Versus Radiotherapy Plus Concomitant Chemo or Cetuximab in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. A Randomized Phase III Factorial Study.


Phase 3
18 Years
N/A
Open (Enrolling)
Both
LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

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Trial Information

Neoadjuvant Docetaxel Plus Cisplatin and 5-fluorouracil (TPF) Followed by Radiotherapy Plus Concomitant Chemo or Cetuximab Versus Radiotherapy Plus Concomitant Chemo or Cetuximab in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. A Randomized Phase III Factorial Study.


This multicenter open label randomised phase III study is the implementation of a previous
phase II randomized trial evaluating the efficacy of chemoradiotherapy with or without
neoadjuvant TPF chemotherapy in locally advanced Head and Neck cancer. Assuming a
randomisation ratio of 1:1, using the Mantel-Cox version of the log-rank test, 204 events
are required in order to achieve a power of 0.80 of detecting an hazard ratio of 0.675 in
favour of the experimental treatment with a type I error of 0.05, two-sided. With a uniform
accrual of 4 years and a follow-up of 2 further years, the total number of required patients
is 420 (210 per arm) to detect an absolute difference of 12% in 3 year overall survival in
favour of the neoadjuvant arm (from 52.5% to 64.5%).Since the 101 patients randomized in the
phase II part of the study will be included in the final analysis, 319 new patients are
needed to complete the trial.The total number of 420 patients will be able to detect a
difference of 10%, (from 35% to 45%) in terms of grade 3/4 in-field mucosal toxicity during
the concomitant treatment (radiotherapy plus chemo or cetuximab) with a power of 80%. Within
the H&N07 trials was introduced a sub-study that allows to investigate the value of
circulating marker evaluation as predictor of response to anti EGFR therapy in patients with
cancer of the head and neck.

The expression level analysis of circulating biological markers will be evaluated on blood
collected during therapy. The analysis will concern the following biological
markers:Cytokines angiogenesis and cell adhesion molecules; Proteins involved in the EGFR
signaling pathway (EGF, TGF-a, s-EGFR);circulating tumor cells (CTC) and circulating
endothelial cells (CEC).


Inclusion Criteria:



1. Histologically or cytologically proven squamous cell carcinoma of the head and neck.

2. Primary tumor sites eligible : oral cavity, oropharynx, hypopharynx Although
they are admittedly of squamous cell types, the following tumors will be excluded
because of them responsiveness to chemotherapy: tumors of the nasal and paranasal
cavities and of the nasopharynx.

3. Stage 3 or 4 disease without evidence of distant metastases verified by chest X Ray,
abdominal ultrasound, or CT (liver function test abnormalities); bone scan in case of
local symptoms.

4. At least one uni or bidimensionally measurable lesion.

5. Tumor considered inoperable after evaluation by a multidisciplinary team (i.e. a
surgeon, a medical oncologist and a radiation oncologist). Criteria for
inoperability are:

1. technical unresectability: tumor fixation/invasion to base of the skull or
cervical vertebrae, involvement of the nasopharynx, and fixed lymph nodes.

2. Physician decision based on low surgical curability. This category will include
the following:

i) All T3-4 stages. ii) All N2-3 stages excluding T1 N2. iii) Patients for organ
preservation. Reason for inoperability will be recorded in the CRF.

6. No previous chemotherapy or radiotherapy for any reason and no previous surgery for
SCCHN (other than biopsy) are allowed at time of study entry.

7. Age > 18 years.

8. Karnofsky performance status > 70. (ECOG 0-1) (Appendix II)

9. No active alcohol addiction.

10. Life expectancy > 6 months.

11. Signed informed consent prior to beginning protocol specific procedures.

12. Adequate bone marrow, hepatic and renal functions as evidenced by the following:

a) Hematology (Bone marrow): i) Neutrophils > 2.0 109/L ii) Platelets > 100 x 109/L
iii) Hemoglobin > 10 g/dL b) Hepatic function i) Total bilirubin < 1 x UNL ii) ASAT
(SGOT) and ALAT (SGPT) < 2.5 x ULN iii) Alkaline phosphatase < 5 x ULN Patients with
ASAT or ALAT > 1.5 x ULN associated with alkaline phosphatase > 2.5 x ULN are not
eligible for the study.

c) Renal function : serum creatinine < 1 x UNL. In case of borderline value the
creatinine clearance > 60 ml/min (calculated by the Cockcroft-Gault method as follows
:

13. Patients must be available for treatment and follow-up. Patients registered on this
trial must be treated and followed at the participating center.

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Exclusion Criteria:

1. Pregnant or lactating women or women of childbearing potential not using adequate
contraception.

2. Previous or current malignancies at other sites, with the exception of adequately
treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of
the skin, or other cancer curatively treated by surgery and with no evidence of
disease for at least 5 years. Any prior treatment with radiotherapy or chemotherapy
is an exclusion criterion.

3. Symptomatic peripheral neuropathy > grade 2 by NCIC-CTG criteria

4. Symptomatic altered hearing > grade 2 by NCIC-CTG criteria.

5. Other serious illnesses or medical conditions including:

1. Unstable cardiac disease despite treatment, myocardial infarction within 6
months prior to study entry.

2. History of significant neurologic or psychiatric disorders including dementia or
seizures.

3. Active uncontrolled infection.

4. Active peptic ulcer.

5. Hypercalcemia.

6. Chronic obstructive pulmonary disease requiring hospitalization during the year
preceding study entry

6. History of hypersensitivity reaction to polysorbate 80 (Appendix IV)

7. Patients requiring intravenous alimentation.

8. Patients who experienced a weight loss of more than 20% of their body weight in the 3
months preceding study entry.

9. Concomitant treatment with any other anticancer therapy.

10. Participation in a therapeutic clinical trial within 30 days of study entry

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

overall survival

Outcome Description:

overall survival defined as the time from the date of randomization to the date of death from any cause.

Outcome Time Frame:

3 years

Safety Issue:

No

Authority:

Italy: The Italian Medicines Agency

Study ID:

H&N07

NCT ID:

NCT01086826

Start Date:

March 2008

Completion Date:

November 2013

Related Keywords:

  • LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

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